Apparatus and Method For Detecting Amyloid In A Retina in a Diagnosis, Advancement, and Prognosing Of Alzheimer&#39;s disease, traumatic brain injury, macular degeneration and a plurality of Neurodegenerative dissorders, and Ocular Diseases

ABSTRACT

The present invention is an apparatus and method to produce an image of an eye of a patient that includes an optical head that includes imaging optics, illumination source optics and a camera housing with a perimeter that houses the video camera optics and the illumination source optics, a slit lamp chinrest and joystick assembly that includes an adjustable head support, a movable base, a joystick that adjusts a position of the camera housing relative to the head support and the housing support that mounts the video camera, a rubber eyecup that provides an interface between the camera housing and the patient&#39;s eye that protrudes outward from the perimeter and a computer system that analyzes images and data for the presence of amyloid in a retina, and other deposits and provides a diagnosis of macular degeneration, Alzheimer&#39;s disease, traumatic brain injury, multiple concussive injury, neurodegenerative and other ocular disorders.

This application claims priority to U.S. Provisional Application61/406,551 filed on Nov. 25, 2010, the entire disclosure of which isincorporated by reference.

TECHNICAL FIELD & BACKGROUND

Imaging of amyloid-beta plaques (including amyloid, amyloid-betapeptides) and other pathology and anatomical features in the retina orbrain is often unobtainable without the use of specialized contrastagents, or autofluorescence techniques. While drusen and amyloidcontaining plaques may be visible in the retina with a variety ofimaging techniques, specifically amyloid-beta plaques (including amyloidin other forms such as amyloid peptides) located in drusen, or otheramyloid containing plaques (or in the retina or fundus at large) are notvisible and verifiable as containing amyloid with any retinal imagingmodalities with the sole exception of curcumin fluorescence/reflectanceimaging that has been performed in vivo in animals only.

The apparatus and method can be used for the detection of amyloid in theretina and brain. This can be achieved solely with OCT by identificationof a spectral signature of an amyloid in an OCT data set and or theanatomic location of plaques. The detection can also be achieved byvarying the wavelength of the OCT device and analyzing the generatedsignal to derive an amyloid signal. This can also be achieved by acombination of OCT with multispectral imaging or the use ofmultispectral imaging alone or the use of autofluorescence or a contrastagent together with OCT. In each of the modalities the spectralsignature can be obtained by spectral analysis and image processing. Theimage processing can identify the spectral wavelength and the spectralsignature identified with amyloid in the retina and the brain usingimage processing techniques.

The apparatus and method utilizes a plurality of traditional opticalcoherence tomography (OCT) and current fundus imaging techniques for thevisualization of amyloid in the retina or the brain through acombination of optical technology in combination with spectral analysisand image processing. By operating a plurality of OCT and multispectralimaging devices at a plurality of specific wavelengths a spectralsignature of amyloid-beta plaques are allowed to be obtained from a dataset utilizing image processing.

The apparatus and method utilizes a plurality of different operatingmodes and configurations such as a hand-held instrument or a mountedslit lamp, an integrated slit lamp, an integrated fundus camera, ascanning laser ophthalmoscope, or an optical head (such as a funduscamera) attached to a separate chinrest-joystick assembly.

The apparatus and method utilizes OCT and/or multispectral imaging incombination with standard or proprietary spectral wavelength selection,spectral analysis, and image processing to identify amyloid in theretina (or brain) rendering it visible to a clinician.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will be described by way of exemplary embodiments,but not limitations, illustrated in the accompanying drawing in whichlike references denote similar elements, and in which:

FIG. 1A illustrates a side perspective view of an apparatus for imagingan eye, in accordance with one embodiment of the present invention.

FIG. 1B illustrates a side perspective view of a camera assembly, inaccordance with one embodiment of the present invention.

FIG. 1C illustrates a front overhead perspective view of an eyecup, inaccordance with one embodiment of the present invention.

FIG. 1D is an exploded diagonal side perspective diagram of a computersystem, in accordance with one embodiment of the present invention.

FIG. 2 illustrates a side perspective view of an apparatus for imagingan eye utilized in combination with a microscope, in accordance with oneembodiment of the present invention.

FIG. 3 illustrates a side perspective view of an apparatus for imagingan eye that is hand-held, in accordance with one embodiment of thepresent invention.

FIG. 4 is a block diagram of various components that can be utilized incombination with an apparatus for imaging an eye, in accordance with oneembodiment of the present invention.

FIG. 5 is a method for diagnosing an eye disease in a mammal, inaccordance with one embodiment of the present invention.

FIG. 6 is a method for diagnosing an eye disease in a mammal, inaccordance with one embodiment of the present invention.

FIG. 7 is a method for diagnosing an eye disease in a mammal, inaccordance with one embodiment of the present invention.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

Various aspects of the illustrative embodiments will be described usingterms commonly employed by those skilled in the art to convey thesubstance of their work to others skilled in the art. However, it willbe apparent to those skilled in the art that the present invention maybe practiced with only some of the described aspects. For purposes ofexplanation, specific numbers, materials and configurations are setforth in order to provide a thorough understanding of the illustrativeembodiments. However, it will be apparent to one skilled in the art thatthe present invention may be practiced without the specific details. Inother instances, well-known features are omitted or simplified in ordernot to obscure the illustrative embodiments.

Various operations will be described as multiple discrete operations, inturn, in a manner that is most helpful in understanding the presentinvention. However, the order of description should not be construed asto imply that these operations are necessarily order dependent. Inparticular, these operations need not be performed in the order ofpresentation.

The phrase “in one embodiment” is used repeatedly. The phrase generallydoes not refer to the same embodiment, however, it may. The terms“comprising”, “having” and “including” are synonymous, unless thecontext dictates otherwise.

FIG. 1A illustrates an exploded perspective view of an apparatus 100 forproducing an image of an eye, in accordance with one embodiment of thepresent invention. The image is an image of an amyloid-beta plaque, anamyloid or an amyloid-beta peptide or other pathology or anatomicalfeatures in the eye or brain of a user. The apparatus 100 detects theamyloid-beta plaque, the amyloid or the amyloid-beta peptide by aspectral signature. The apparatus 100 performs a maximum and minimumintensity projection (MIP/MinIP).

The apparatus for producing an image of an eye 100 includes a videocamera 110, video camera optics 112, a camera housing 120 mounted on aslit lamp chinrest and joystick assembly 130 and illumination sourceoptics 140. The video camera 110 is a digital camera but can be any typeof suitable camera for use with the apparatus for producing an image ofan eye 100. The slit lamp chinrest and joystick assembly 130 includes ahead support 142, a movable base 144, a joystick 146, and a housingsupport 148. The head support 142 holds the patient's chin and foreheadin a known, fixed position. The head support 142 is provided with aplurality of elevation adjustments to provide a comfortable restingplace for the patient's head. The position of the camera housing 120relative to the head support 142 can be adjusted in both relative grossand fine increments using the joystick 146. The apparatus for producingan image of an eye 100 is used in combination with a computer system150, which is described in greater detail in FIG. 1D. The computersystem 150 can be any suitable computer system 150 that can be used incombination with the apparatus for imaging an eye 100.

The personal computer 150 forms the center of the apparatus for imagingan eye 100, processing data and controlling the operation of othercomponents of the apparatus for imaging an eye 100. Connected to thepersonal computer 150 is a video camera 110. An observation videomonitor which can be the screen of the personal computer, a slit lampchinrest and joystick assembly 130, illumination source optics 140, andvideo camera optics 112 are associated with the camera housing 120.

The personal computer 150 is a relatively compact computer, embeddedcomputer, or tablet computer of relatively high processing power using astandardized operating system and having standardized card slots forinterfacing peripheral equipment such as memory cards, video board,printer and a monitor. The personal computer 150 will run customizedsoftware as will be described in detail later. The monitor or screen ofthe personal computer will have very-high-resolution color graphicscapability appropriate for displaying images under analysis.

The digitizing board accepts a digital file or video input from videocamera 110 and functions as a “frame grabber,” or display. That is, whenactivated by a signal from the personal computer 150, the digitizingboard will collect video and/or digital data and images from videocamera 110 at that instant and store into digital data. The digital dataproduced is stored in memory and made available to personal computer 150for analysis.

FIG. 1B illustrates a side perspective view of a camera housing 120 ofthe chinrest and joystick assembly 130, in accordance with oneembodiment of the present invention. The camera housing 120 containingthe video camera 110 illumination source(s) and optics 140 is proximateto a sectioned patient eyeball EB with a cornea C and a retina R.Housing 120 may be cylindrical or of any other suitable shape. Thehousing 120 has no forward protruding parts, which prevents accidentaldirect contact of any part of the apparatus for imaging an eye 100 withthe patient's cornea C or facial features during movement of the housing120 relative to the patient's eyes. This is advantageous since there isno contact with the patient's cornea C to accomplish examination andimage capture. The external housing 120 and the optics have beendesigned to maintain some distance to the cornea C, increasing patientcomfort while any testing is being performed. A flexible interface suchas a rubber cup 180 can be provided at the interface between the housing120 and the patient's eyeball EB.

The inclusion of illumination source optics 140, camera optics 112 andthe video camera 110 in the camera housing 120 provides a high degree ofaccessibility. By placing all elements of the apparatus for imaging aneye 100 in one camera housing 120, allows for an affordable design.Additionally, the relatively small design of the apparatus for imagingan eye 100 compared to that of a fundus camera for observation and imagecapture provides for a shorter and more efficient optical pathway. Thecompact design and simplicity of optics 112,140 reduces production costsand permits greater ease of use by the operator. The design of theapparatus for imaging an eye 100 allows imaging through a smaller pupilas compared to a fundus camera.

Video camera 110 is relatively compact and incorporates a color ormonochrome CCD, CMOS, or multi/hyper-spectral image sensor. The focus ofthe patient may also be achieved by focus of internal optical elementsof the digital camera. Lens contained inside camera 100 may be focusedautomatically or manually by observing the image displayed on anobservation video monitor. Alternatively, an electronic auto-focusingcontrol system could be provided for automatically adjusting the focusof lens inside camera 100. The video camera 110 can also contain amonochrome or color CCD or CMOS sensor (not shown).

The observation optics 112 associated with the video camera 110 includethe lens 170, an observation aperture 172, and a filter 174. Theobservation aperture 172 and the filter 174 transmit light reflectedfrom the retina R to the lens 170 and to the video camera 110. Thefilter 174 is an infrared stepping filter (or other filter for otherimaging procedures) which improves the contrast of the image seen by thevideo camera 110.

Indo-cyanine green angiography, color fundus photography,auto-fluorescence, or fluorescein angiography, curcumin fluorescenceimaging, or other filter sets may be utilized by the apparatus forimaging an eye 100. These filters will be mounted so as to beselectively rotatable in and out of the view axis of the video camera110 according to the function being performed. The rotation may beaccomplished manually or under computer servo control.

The projection optics 140 of the invention projects light onto theretina R, off axis at an angle to the central axis 176 of lens 170 ofvideo camera 110. The projection optics 140 includes a lamp 141, a lamplens group 143, a mirror 145, and a projection aperture 172. A control1001 is provided to adjust the intensity and position of the lamp 141,either manually or under the control of the computer system 150. Thecontrol is also used to sequentially control multiple lamps 141,shifting optical elements, and flipping masks 147, LED flipping internalfixation pointer 1004, and image capture trigger.

The light from lamp 141 passes through aperture 149 and the series oflamp lens group 143 that typically has two lenses. The lenses of lamplens group 143 concentrate the light output of lamp 141. Lamp lens group143 may consist of multiple lenses or a single aspheric lens. The lightis then deflected by mirror 145 which is placed at a critical pitchangle relative to the video camera 110 and the projection optics 112.The light passes from the mirror 145 past the flipping mask 147 whichconcentrates the light. The light then passes through a plurality ofsmall pupil masks 1002. The light then passes through the objective lens1003. The light then passes past the cornea C and is projected ontoretina R.

All the masks and apertures used, such as flipping mask 147 and aperture149 and 1002, are appropriately sized apertures. Although the lamp 141has been described as a generalized LED lamp, it should be noted thatthe lamp 141 can be any source of radiant energy. In one embodiment, thelamp 141 is an infrared illumination source, and the specifications offilter 174 are adjusted accordingly to pass the wavelength of the lamp141. Infrared illumination may be particularly desirable for alignmentprior to acquiring images without the problems generated by lack ofpupil dilation. The image can be captured in a relatively dark roomusing infrared illumination, so that the eye being imaged is naturallydilated. There is also a means for sequentially turning the light sourceon and off in synchronization with image capture under each condition,which is a computer system 150, further described in FIG. 1C.

In another embodiment which addresses the problems caused by lack ofpupil dilation during imaging, the lamp 141 may be strobed in fullcolor, red free, NIR or other wavelength (based on imaging proceduredesired) during image acquisition rather than being kept on constantly,thereby preventing the energy of lamp 141 from narrowing the pupil priorto image capture. Because of the unique design of the projection optics140 and the capabilities of the image processing and analysis softwareemployed, useful image data from each image can be collected withminimum pupil dilation. Specifically, the pupils of the eye being imagedmay have a diameter of as little as 2 mm. The projection optics 140projects light onto the retina R off axis from the observation path ofvideo camera 110. Another embodiment places an adjustable mask 1002adjacent to objective lens 1003 that adjust to the patient's pupil tooptimize the image when the pupil is small.

FIG. 1C illustrates a front overhead perspective view of an eyecup 180,in accordance with one embodiment of the present invention. The eyecup180 protrudes outward from the perimeter 182 at an approximate 10%increase at the approximate 0° 184 and 180° degree 186 positions on theperimeter 182. Further details regarding the eyecup 180 are described inFIG. 3 and its description.

FIG. 1D is an exploded diagonal side perspective diagram of a computersystem 150, in accordance with one embodiment of the present invention.Such a computer system 150 includes a processing unit such as a CPU 151connected by a bus to a random access memory or RAM 152, a storagedevice 153, a keyboard 154, a display 155 and a mouse 156. In addition,there is software 157 for entry of data embodying the apparatus forimaging an eye 100. An example of a computer system 150 can be a Dellpersonal computer operating on the Microsoft Windows operating system,or Linux, Macintosh, etc. The invention can also be used on a laptopcomputer, cell phone, PDA, Apple™ Mac™, tablet, or other computerizeddevice. The computerized system 150 can also be used in combination witha wireless modem 158 or network interface card 159.

The various method embodiments of the invention will be generallyimplemented by a computer executing a sequence of program instructionsfor carrying out the steps of the method, assuming all required data forprocessing is accessible to the computer. The sequence of programinstructions may be embodied in a computer program product comprisingmedia storing the program instructions. As will be readily apparent tothose skilled in the art, the present invention can be realized inhardware, software, or a combination of hardware and software. Any kindof computer/server system(s) or other apparatus adapted for carrying outthe methods described herein is suited. A typical combination ofhardware and software could be a general-purpose computer system with acomputer program that, when loaded and executed, carries out the method,and variations on the method as described herein.

Any combination of one or more computer usable or computer readablemedium(s) may be utilized. Specific examples of the computer-readablemedium can include a hard disk, a random access memory (RAM), aread-only memory (ROM), an erasable programmable read-only memory(EPROM), or flash memory or a portable compact disc read-only memory(CD-ROM). In the context of this document, a computer-usable orcomputer-readable medium may be any medium that can be used by or inconnection with the instruction execution system or apparatus. Computerprogram code for carrying out operations of the overall method may bewritten in any combination of one or more programming languages. Theprogram code may execute entirely on the user's computer, partly on theuser's computer, as a stand-alone software package, partly on the user'scomputer and partly on a remote computer or entirely on the remotecomputer or server.

These computer program instructions may also be stored in acomputer-readable medium that can direct a computer or otherprogrammable data processing apparatus to function in a particularmanner, such that the instructions stored in the computer readablemedium produce an article of manufacture including instructions meanswhich implement the function specified in the steps.

The computer program instruction may also be loaded onto a computer orother programmable data processing apparatus to cause a series ofoperational steps to be performed on the computer or other programmableapparatus to produce a computer implemented process such that theinstructions which execute on the computer or other programmableapparatus provide processes for implementing the functions specified.

FIG. 2 illustrates a side perspective view of an apparatus for imagingan eye 200 utilized in combination with a microscope 260, in accordancewith one embodiment of the present invention. FIG. 2 illustrates a sideperspective view of an apparatus for imaging an eye 100 that has all ofthe same components of the apparatus for imaging an eye 100 described inFIG. 1A, except the microscope 260 and the computer system 150. Theapparatus for producing an image of an eye 200 includes a video camera210, video camera optics 212, a camera housing 220 mounted on a patientalignment assembly 230 and illumination source optics 240. Themicroscope assembly 230 includes a support 242, a movable base 244, andhousing support 248. The position of the camera housing 220 relative tothe head support 242 can be adjusted in both gross and fine incrementsusing the joystick 246. The microscope 260 can be any suitablemicroscope that can be used in combination with the apparatus forimaging an eye 200.

In one embodiment of the apparatus and method, OCT data is presentedwith traditional OCT display modalities and/or en face to produce aplurality of familiar retinal images.

In one embodiment of the apparatus and method, OCT is performed using aplurality of specific wavelengths that allow for the visualization ofamyloid in the retina and the brain. A plurality of OCT data sets areobtained and analysis is performed to identify a plurality of spectralsignature components of the amyloid. These spectral components thatcorrespond to the amyloid are subsequently displayed in the OCT datasets that include an en face presentation. Spectral signalcharacteristics can be combined with other specific spectral componentsto render traditional OCT data sets in combination with the amyloidspectral data set.

In another embodiment of the apparatus and method, a minimum thresholdtechnique in combination with an adaptive spectral windowing techniqueis applied to the data sets to render visualization of previous unseenfeatures in the OCT data sets. In another embodiment of the apparatusand method, this technique is applied to not only amyloid but also otherpathology and also anatomical features of the retina.

In another embodiment of the apparatus and method, the OCT device isoperated at a plurality of different and specific spectral wavelengthsto tease out desired signature and information.

In another embodiment of the apparatus and method, the apparatus andmethod utilizes multispectral imaging to image amyloid and other retinalpathology and features without the use of dyes or contrast agents. Inanother embodiment of the apparatus and method, this is accomplished viaoptical multispectral imaging and/or autofluorescence techniques inwhich the specific amyloid signal is identified and presented.

In another embodiment of the apparatus and method, curcumin (which bindsto the amyloid) is used as a contrast agent in combination with OCT todiscreetly identify the amyloid. In another embodiment of the apparatusand method, curcumin is used as a contrast agent in combination withmultispectral optical and/or autofluorescence imaging to discreetlyidentify amyloid in the retina.

Another embodiment of the apparatus and method, includes a method ofdiagnosing macular degeneration and other eye diseases in a mammal thatadministers a fluorescent marker to the mammal for staining A[beta]peptides, imaging the mammal's retina with optical coherence tomographyOCT, examining the data sets for stained A[beta] peptides and diagnosingthe mammal as having macular degeneration or another eye disease ifstained A[beta] peptides are present.

Another embodiment of the apparatus and method, wherein a fluorescentmarker is selected from the group including but not limited to curcumin,curcumin derivatives, Thioflavin S and derivatives, Thioflavin T andderivatives, Congo Red and derivatives, methoxy-X04, Pittsburgh CompoundB (PiB), DDNP, Chrysamine-G and combinations thereof.

Another embodiment of the apparatus and method, wherein the OCT systemis used with components including a spectrometer, a fluorescencemicroscope, a stereomicroscope, a mercury arc lamp, a variablewavelength light source, a xenon arc lamp, and LED, a tunable lightsource or swept source, a CCD gated camera, a color digital camera, anacoustic-optic tunable filter-based spectral image acquisition system,adaptive optics, imaging software, and combinations thereof.

Another embodiment of the apparatus and method, for the prognosing ofmacular degeneration and other eye disease in a mammal that includesidentification of A[beta] peptides, imaging the subject's retina withOCT and/or multispectral imaging/autofluorescence, examining the imagesfor A[beta] peptides, quantitating the increase/decrease of A[beta]peptides in the subject's retina, as compared to a prior diagnosis andrendering a prognosis based upon the level of A[beta] peptides in thesubject's retina including but not limited to number, area and volume.

Another embodiment of the apparatus and method, for the prognosing ofmacular degeneration and other eye disease in a mammal that includesidentification of A[beta] peptides, imaging the subject's retina withOCT and/or multispectral imaging/autofluorescence, examining the imagesfor A[beta] Peptides, quantitating the increase/decrease of A[beta]peptides in the subject's retina, as compared to a prior diagnosis incombination with a normative database and rendering a prognosis basedupon the level of A[beta] peptides in the subject's retina (includingbut not limited to number, area and volume).

Another embodiment of the apparatus and method, for the prognosing oftraumatic brain injury and other neurodegenerative disease in a mammalthat includes identification of A[beta] peptides, imaging the subject'sretina with OCT and/or multispectral imaging/autofluorescence, examiningthe images for A[beta]

Peptides, quantitating the increase/decrease of A[beta] peptides in thesubject's retina, as compared to a prior diagnosis in combination with anormative database and rendering a prognosis based upon the level ofA[beta] peptides in the subject's retina (including but not limited tonumber, area and volume).

Another embodiment of the apparatus and method, is to perform aMaximum/Minimum Intensity Projection (MIP/MiniP) and/or in combinationwith other specific discreet spectral signatures on OCT and/ormultispectral images for the identification of amyloid in the retina (orbrain) and other retinal features and pathology including but notlimited to choroidal neovascularization. Maximum intensity projection(MIP) and minimum intensity projection (MiniP) are defined as volumerendering techniques in which suitable editing methods are used todefine a volume of interest (VOI). All of the image data set may beused, or the volume may be confined to a region of interest (ROI).

In one embodiment of the apparatus and method, only desired features areincluded or excluded from the VOI and actual images are generated byprojecting the volume of interest into a viewing plane and displayingthe maximum OCT scan numbers (for MIP) or the minimum OCT numbers (forMiniP) that are encountered along the direction of the projection toensure that optimum contrast is produced between small, high-contraststructures and surrounding tissues.

FIG. 3 illustrates a side perspective view of a hand held apparatus forimaging an eye 300, in accordance with one embodiment of the presentinvention. The hand held apparatus for imaging an eye 300 includes allof the same components of the apparatus for imaging an eye 100 describedin FIG. 1B and can be used in combination with a microscope 260 (FIG. 2)or a computer system 150 (FIG. 1A). The hand held apparatus for imagingan eye 300 utilizes a hand-held housing 310 instead of a camera housing120 as described in FIGS. 1A and 1B, but utilizes all of the sameoptical and electrical components disposed within the hand-held housing310.

The hand-held apparatus for producing an image of an eye 300 may alsoutilize a flexible eyecup 320 that could be fixed to the hand-heldapparatus for producing an image of an eye 300, or be utilized as adisposable flexible eyecup that attaches to the end 312 of the apparatusfor producing an image of an eye for use on each patient. The flexibleeyecup 320 could be made of baffled flexible material 322 such asrubber, plastic, or any type of suitable material that gently surroundsthe patient's eye to create a darkened environment and could also beused to hold a patient's eyelids open. The flexible eyecup 320 couldhave an angular spring internal mechanism 330 that holds the patient'seyelids open. The baffles 322 are flexible to allow for adjustable andproper positioning around the patient's eye.

FIG. 4 is a block diagram of a plurality of various components 400 thatcan be utilized in combination with an apparatus for imaging an eye, inaccordance with one embodiment of the present invention.

These components 400 include are selected from the group consisting of aspectrometer 405, a fluorescence microscope 410, a stereomicroscope 415,a mercury arc lamp 420, a variable wavelength light source 425, a xenonarc lamp 430, an LED light 435, a tunable light source or swept source440, a CCD gated camera 445, a color digital camera 450, anacoustic-optic tunable filter-based spectral image acquisition system455, a plurality of adaptive optics 460, imaging software 465 and anycombinations thereof. The apparatus 100 is utilized in combination withone or more contrasting agents that are selected from the groupconsisting of curcumin, curcumin derivatives, Thioflavin S andderivatives, Thioflavin T and derivatives, Congo Red and derivatives,methoxy-X04, Pittsburgh CompoundB (PiB), DDNP, Chrysamine-G and anycombination thereof.

FIG. 5 is a method 500 for diagnosing an eye disease in a mammal, inaccordance with one embodiment of the present invention.

The steps of the method 500 include administering a contrasting agent tothe mammal to stain one or more A[beta] peptides 510, imaging themammal's retina with optical coherence tomography 520, examining aplurality of data sets from the stained A[beta] peptides 530 anddiagnosing the mammal as having the eye disease if the stained A[beta]peptides are present 540. The administering a contrasting agent to themammal to stain one or more A[beta] peptides 510 can be accomplishedwith one or more contrasting agents are selected from the groupconsisting of curcumin, curcumin derivatives, Thioflavin S andderivatives, Thioflavin T and derivatives, Congo Red and derivatives,methoxy-X04, Pittsburgh CompoundB (PiB), DDNP, Chrysamine-G and anycombination thereof. The imaging the mammal's retina with opticalcoherence tomography 520 can be accomplished with the apparatus toproduce an image of an eye of a patient that is previously described inFIGS. 1A and 1B and its components that include a digital video camerathat includes video camera optics, illumination source optics and acamera housing with a perimeter that houses the video camera optics andthe illumination source optics, a slit lamp chinrest and joystickassembly that includes an adjustable head support, a movable base, ajoystick that adjusts a position of the camera housing relative to thehead support and the housing support that mounts the video camera, arubber eyecup that provides an interface between the camera housing andthe patient's eye that protrudes outward from the perimeter and acomputer system. The examining a plurality of data sets from the stainedA[beta] peptides 530 is accomplished typically with the computer systempreviously described in FIG. 1D. The diagnosing the mammal as having theeye disease if the stained A[beta] peptides are present 540 isstraightforwardly an indication characteristic of the stained A[beta]peptides.

FIG. 6 is a method 600 for diagnosing an eye disease in a mammal, inaccordance with one embodiment of the present invention.

The method 600 includes administering a fluorescent marker to the mammalto stain one or more A[beta] peptides 610, imaging the mammal's retinawith optical coherence tomography 620, examining a plurality of datasets from the stained A[beta] peptides 630 and quantitating an increaseor decrease of the A[beta] peptides in the mammal's retina and renderinga prognosis based upon a level of the A[beta] peptides 640.

The administering a contrasting agent to the mammal to stain one or moreA[beta] peptides 610 can be accomplished with one or more contrastingagents are selected from the group consisting of curcumin, curcuminderivatives, Thioflavin S and derivatives, Thioflavin T and derivatives,Congo Red and derivatives, methoxy-X04, Pittsburgh CompoundB (PiB),DDNP, Chrysamine-G and any combination thereof. The imaging the mammal'sretina with optical coherence tomography 620 can be accomplished withthe apparatus to produce an image of an eye of a patient that ispreviously described in FIGS. 1A and 1B and its components that includea digital video camera that includes video camera optics, illuminationsource optics and a camera housing with a perimeter that houses saidvideo camera optics and said illumination source optics, a slit lampchinrest and joystick assembly that includes an adjustable head support, a movable base, a joystick that adjusts a position of said camerahousing relative to said head support and the housing support thatmounts the video camera, a rubber eyecup that provides an interfacebetween the camera housing and the patient's eye that protrudes outwardfrom the perimeter and a computer system. The examining a plurality ofdata sets from the stained A[beta] peptides 630 is accomplishedtypically with the computer system previously described in FIG. 1D. Thequantitating an increase or decrease of the A[beta] peptides in themammal's retina and rendering a prognosis based upon a level of theA[beta] peptides 640 is accomplished typically with the computer systempreviously described in FIG. 1D.

FIG. 7 is a method 700 for diagnosing an eye disease in a mammal, inaccordance with one embodiment of the present invention.

The method 700 includes administering a fluorescent marker to the mammalto stain one or more A[beta] peptides 710, imaging the mammal's retinawith optical coherence tomography 720, examining a plurality of datasets from the stained A[beta] peptides 730 and quantitating an increaseor decrease of the A[beta] peptides in the mammal's retina as comparedto a prior diagnosis in combination with a normative database andrendering a prognosis based upon a level of the A[beta] peptides 740.

The administering a contrasting agent to the mammal to stain one or moreA[beta] peptides 710 can be accomplished with one or more contrastingagents are selected from the group consisting of curcumin, curcuminderivatives, Thioflavin S and derivatives, Thioflavin T and derivatives,Congo Red and derivatives, methoxy-X04, Pittsburgh CompoundB (PiB),DDNP, Chrysamine-G and any combination thereof. The imaging the mammal'sretina with optical coherence tomography 720 can be accomplished withthe apparatus to produce an image of an eye of a patient that ispreviously described in FIGS. 1A and 1B and its components that includea digital video camera that includes video camera optics, illuminationsource optics and a camera housing with a perimeter that houses saidvideo camera optics and said illumination source optics, a slit lampchinrest and joystick assembly that includes an adjustable head support, a movable base, a joystick that adjusts a position of said camerahousing relative to said head support and the housing support thatmounts the video camera, a rubber eyecup that provides an interfacebetween the camera housing and the patient's eye that protrudes outwardfrom the perimeter and a computer system. The examining a plurality ofdata sets from the stained A[beta] peptides 730 is accomplishedtypically with the computer system previously described in FIG. 1D. Thequantitating an increase or decrease of the A[beta] peptides in themammal's retina as compared to a prior diagnosis in combination with anormative database and rendering a prognosis based upon a level of theA[beta] peptides 740.

While the present invention has been related in terms of the foregoingembodiments, those skilled in the art will recognize that the inventionis not limited to the embodiments described. The present invention canbe practiced with modification and alteration within the spirit andscope of the appended claims. Thus, the description is to be regarded asillustrative instead of restrictive on the present invention.

1. An apparatus to produce an image of an eye of a patient, comprising:an optical head that includes a digital camera, a plurality of imagingoptics, a plurality of illumination source optics and a camera housingwith a perimeter that houses said optical head optics and saidillumination source optics; a slit lamp chinrest and joystick assemblythat includes an adjustable head support, a movable base, a joystickthat adjusts a position of said camera housing relative to said headsupport and said housing support that mounts said optical head; ahand-held assembly that includes an optical head and a hand grip foroperation; a rubber eyecup that provides an interface between saidcamera housing and said patient's eye that protrudes outward from saidperimeter to hold eye lids open; and a computer system that includes alive viewing window that displays a live video, provides a plurality ofalignment aids, processes data, and controls said apparatus that is incommunication with said optical head and said video camera and saidillumination source optics.
 2. The apparatus according to claim 1,wherein said rubber eyecup protrudes at an approximate 10% increase atan approximate 0 degree and an approximate 180 degree position to holdsaid patient's eye lids open.
 3. The apparatus according to claim 1,wherein said computer system is a compact computer, a smart phone, anembedded computer, or a tablet computer.
 4. The apparatus according toclaim 1, wherein said digitized video board collects a plurality ofvideo or digital data and images from said video camera and stores saidvideo and said data to be analyzed and processed into one or moreplenoptic images, combining a plurality of in focus elements from aplurality of individual images thereby increasing resolution and imagequality.
 5. The apparatus according to claim 1, wherein said apparatusis utilized in an autofluorescence mode and in combination with one ormore contrast agents.
 6. The apparatus according to claim 5, whereinsaid contrasting agents are selected from the group consisting ofcurcumin, curcumin derivatives, Thioflavin S and derivatives, ThioflavinT and derivatives, CRANAD 3, Fluorescein, Indocyanine Green, Congo Redand derivatives, methoxy-X04, Pittsburgh CompoundB (PiB), DDNP,Chrysamine-G and any combination thereof.
 7. The apparatus according toclaim 1, wherein said apparatus is utilized in combination with one ormore components that are selected from the group consisting of aspectrometer, a fluorescence microscope, a stereomicroscope, a mercuryarc lamp, a variable wavelength light source, a xenon arc lamp, an LEDlight, a tunable light source or swept source, a CCD gated camera, acolor digital camera, an acoustic-optic tunable filter-based spectralimage acquisition system, a plurality of adaptive optics, imagingsoftware and any combinations thereof.
 8. The apparatus according toclaim 1, wherein said apparatus is utilized in combination with opticalcoherence tomography, fluorescein and indocyanine green angiography. 9.The apparatus according to claim 1, wherein said image displays anamyloid-beta plaque, an amyloid, a drusen, an amyloid containingdeposit, or an amyloid-beta peptide.
 10. The apparatus according toclaim 9, wherein said apparatus detects said amyloid-beta plaque, saidamyloid, said drusen, said amyloid containing deposit, or saidamyloid-beta peptide by a spectral reflectance signature.
 11. Theapparatus according to claim 1, wherein said apparatus performs amaximum and minimum intensity projection from optical coherencetomography, autofluorescence, curcumin imaging, fluorescein andindocyanine angiography, red-free imaging and multispectral data sets toisolate said amyloid-beta plaque, said amyloid, said drusen, saidamyloid containing deposit, or said amyloid-beta peptide.
 12. A methodfor diagnosing an eye disease in a mammal, comprising: administeringcurcumin, curcumin analogs or other fluorescent dye, probe or marker viaoral consumption, topical eye drop, or intravenous injection to saidmammal to bind to and stain one or more A[beta] peptides; imaging saidmammal's retina with curcumin fluorescence imaging, autofluorescence,multi-spectral imaging, hyperspectral imaging, Fluorescein angiography,ICG angiography and/or optical coherence tomography; examining aplurality of data sets from said A[beta] peptides; and diagnosing saidmammal as having said eye disease if said stained A[beta] peptides,drusen, plaques or deposits are present.
 13. A method for diagnosing aneye disease in a mammal, comprising: administering curcumin, curcuminanalogs, or other fluorescent dye, probe or marker via oral consumption,topical eye drop, or intravenous injection to said mammal to bind to andstain one or more A[beta] peptides; imaging said mammal's retina withcurcumin fluorescence, autofluorescence, multi-spectral imaging,hyperspectral imaging, Fluorescein angiography, ICG angiography and/oroptical coherence tomography; and quantitating an increase or decreaseof said A[beta] peptides in said mammal's retina as compared to a priordiagnosis in combination with a normative disease-state database andrendering a prognosis based upon a level of said A[beta] peptides,plaques, or deposits.
 14. A method for diagnosing an Alzheimer's,traumatic brain injury, multiple concussive injury or otherneurodegenerative disease in a mammal, comprising: administeringcurcumin, curcumin analogs, or other fluorescent dye, probe or markervia oral consumption, topical eye drop, or intravenous injection to saidmammal to bind to and stain one or more A[beta] peptides or deposits;imaging said mammal's retina with curcumin fluorescence,autofluorescence, multi-spectral imaging, hyperspectral imaging,Fluorescein angiography, ICG angiography and/or optical coherencetomography; examining a plurality of data sets from said A[beta]peptides; and diagnosing said mammal as having said disease if saidstained A[beta] peptides, drusen, plaques, or deposits are present. 15.A method for diagnosing an Alzheimer's, traumatic brain injury, multipleconcussive injury or other neurodegenerative disease in a mammal,comprising: administering curcumin, curcumin analogs, or otherfluorescent dye, probe or marker via oral consumption, topical eye drop,or intravenous injection to said mammal to bind to and stain one or moreA[beta] peptides or deposits; imaging said mammal's retina with curcuminfluorescence, autofluorescence, multi-spectral imaging, hyperspectralimaging, Fluorescein angiography, ICG angiography and/or opticalcoherence tomography; and quantitating an increase or decrease of saidA[beta] peptides in said mammal's retina as compared to a priordiagnosis in combination with a normative disease-state database andrendering a prognosis based upon a level of said A[beta] peptides.
 16. Amethod for diagnosing an Alzheimer's, traumatic brain injury, multipleconcussive injury or other neurodegenerative disease in a mammal,comprising: imaging said mammal's retina with autofluorescence,multi-spectral imaging, hyperspectral imaging, Fluorescein angiography,ICG angiography and/or optical coherence tomography; examining andanalyzing a plurality of data sets from said A[beta] peptides; anddiagnosing said mammal as having said disease if said A[beta] peptides,plaques, or deposits are present.
 17. A method for diagnosing anAlzheimer's, traumatic brain injury, multiple concussive injury or otherneurodegenerative disease in a mammal, comprising: imaging said mammal'sretina with autofluorescence and optical coherence tomography; examiningand analyzing a plurality of data sets from said A[beta] peptides;analyzing said optical coherence tomography data for location within theretina and determining diagnosis based upon location of amyloid andamyloid containing deposits; quantitating of the presence of saidA[beta] peptides in said mammal's retina as images with autofluorescenceand OCT as compared to a prior diagnosis in combination with a normativedisease-state database and rendering a prognosis based upon a level ofsaid A[beta] peptides; and diagnosing said mammal as having said diseaseif said A[beta] peptides or deposits are present.
 18. A method fordiagnosing an Alzheimer's, traumatic brain injury, multiple concussiveinjury or other neurodegenerative disease in a mammal, comprising:imaging said mammal's retina with autofluorescence; examining andanalyzing a plurality of images and data sets processed to formplenoptic high-resolution images from data sets thereby identifying saidA[beta] peptides, plaques, or deposits; analyzing said autofluorescencedata for confirming diagnosis based upon spectral signature andmorphology of amyloid and amyloid containing deposits; quantitating ofthe presence of said A[beta] peptides in said mammal's retina as imageswith autofluorescence as compared to a prior diagnosis in combinationwith a normative disease-state database and rendering a prognosis basedupon a level of said A[beta] peptides; and diagnosing said mammal ashaving said disease if said A[beta] peptides, plaques, or deposits arepresent.
 19. A method for diagnosing an Alzheimer's, traumatic braininjury, multiple concussive injury or other neurodegenerative disease ina mammal, comprising: imaging said mammal's retina with any combinationof imaging modalities including Curcumin imaging, autofluorescence, OCT,hyperspectral imaging, multispectral imaging, fluorescein angiography,ICG angiography, color fundus imaging, red-free imaging; examining andanalyzing a plurality of images and data sets thereby identifying saidA[beta] peptides, plaques, or deposits; analyzing said data forconfirming diagnosis based upon spectral signature and morphology ofamyloid and amyloid containing deposits; examining and analyzing aplurality of images and data sets processed to form plenoptichigh-resolution images from data sets thereby identifying said A[beta]peptides, plaques, or deposits; quantitating of the presence of saidA[beta] peptides in said mammal's retina as images with autofluorescenceas compared to a prior diagnosis in combination with a normative diseasestate database and rendering a prognosis based upon a level of saidA[beta] peptides; and diagnosing severity of said disease in said mammalbased on the generation of a retina amyloid index comprising informationfrom spectral signature, background reflectance and fluorescence,intensity, raw integrated density, location in retina via OCT,geographic location in one or more specific regions of the retina,morphology, and regional density.
 20. A method for diagnosing anAlzheimer's, traumatic brain injury, multiple concussive injury or otherneurodegenerative disease in a mammal, comprising: imaging said mammal'sretina with ICG angiography, fluorescein angiography, color fundusimaging, and red-free imaging; examining and analyzing a plurality ofimages and data sets thereby identifying said A[beta] peptides, plaques,or deposits; examining and analyzing a plurality of images and data setsprocessed to form plenoptic high-resolution images from data setsthereby identifying said A[beta] peptides, plaques, or deposits;analyzing said data for confirming diagnosis based upon spectralsignature and morphology of amyloid and amyloid containing deposits;quantitating of the presence of said A[beta] peptides in said mammal'sretina as images with ICG angiography as compared to a prior diagnosisin combination with a normative database and rendering a prognosis basedupon a level of said A[beta] peptides; and diagnosing severity of saiddisease in said mammal based on the generation of a retina amyloid indexcomprising information from spectral signature, background and deposit,intensity, raw integrated density, location in retina via OCT,geographic location in specific region of the retina, morphology, andregional density.